It is extremely important to establish the effects of major marijuana components and their metabolites on compositional, structural and functional properties of the genome. The necessity for understanding cannabinoid-induced effects on the genome is clearly relevant to potential alterations in gene expression and possible heritable disorders which may result from the drugs. To approach the problem of cannadinoid-induced changes in the genome our specific aims are to critically assess: 1) Cannabinoid - induced changes in composition and metabolism of chromosomal proteins. Synthesis, turnover and post-translational modifications of histones and nonhistone chromosomal proteins will be studied. 2) Cannabinoid-induced modifications in chromatin structure. 3) Cannabinoid-induced variations in RNA synthesis. Rates of RNA synthesis and transcription of defined genetic sequences will be studied in intact cells, in nuclei and in chromatin. These studies are being carried out in intact animals, with various tissues and cell types being examined and in cultured human cells, both quiescent and proliferating.